Thiamine (vitamin B1) in its diphosphate form is an enzyme cofactor. The biochemistry of this cofactor involves reactions at a carbon side-chain bonded to the 2 position of the thiazolium ion ring. Deprotonation of this carbon side-chain precedes carbon-carbon bond forming reactions involving the holoenzyme. We propose to model the enzyme system. The kinetics of deprotonation of the carbon chain at the 2 position of thiazolium ions are to be studied in aqueous, enzyme-free, buffers. In D2O solutions, deprotonation leads to an intermediate which then is trapped by deuterated electrophiles, i.e., base catalyzed hydrogen-deuterium exchange of the substrate takes place. Such deprotonation reactions can easily be followed by nuclear magnetic resonance spectroscopy. Preliminary experiments using this technique on a thiazolium ion have demonstrated the feasibility of the proposed study and have shown the deprotonation reaction is clearly reaction is clearly subject to general base catalysis. The reactivities of a series of model thiazolium ions are to be studied. We hope to determine the effects of substrate and catalyst structures on the deprotonation reaction. Substrates are designed to provide information about the importance of steric, electronic and intramolecular catalytic effects. Solvent studies are designed to indicate whether deprotonapion takes place in the hydrophobic regions of the apoenzyme. Our nonenzymatic models are designed to provide information on a molecular level about how the vitamin functions in connection with enzymes such as ketolases. We seek a basic molecular understanding.